TRC
Trisomy Risk
Calculator

Purpose of
TRC

Trisomy Risk Calculator (TRC) for trisomy
21 and 18-13 is an online computer tool developed by SBP Soft
2007 S.L. It demonstrates and confirms the huge potential of
prenatal screening for Down's, Edwards and Patau's syndromes
(the most common trisomies), and it can be used to contrast
with risk estimates currently provided by specialized centers.
Under no circumstances is this computer application intended to
substitute or contribute to clinical diagnosis, and on no
account do SBP Soft 2007 S.L., its proprietors or developers
take responsibility for results or decisions derived of its use
in a given patient or group of patients, even if the user has
correctly entered the requested parameters. Trisomy 21 and
18-13 prenatal detection estimates a pregnant woman’s
probability or Risk of carrying a
trisomy-affected fetus, according to her age
and a combination of biochemical markers
(analyzed in maternal blood) and/or an ultrasound (assessed
using a fetal sonogram). When this risk is high the presence or
absence of the suspected trisomy should be confirmed by an
invasive test (chorionic villus sampling, amniocentesis, etc.),
as the risk is only a statistical estimate, not a definite
diagnosis, which accounts for variability in risk estimates
provided by different computer systems.

Important
information

MoM (Multiples of the Median) calculation of the biochemical
markers values (AFP, uE3, Inhibin A, hCG and PAPP-A) can only
be obtained by a specialized Clinical Analysis Laboratory. MoM
values are usually printed in the screening report.

How to use
TRC

The mother’s age at the expected delivery date (EDD) must be
entered in the first text box. It should be indicated with a
decimal number representing the decimal fraction of a month. As
in all the other text boxes, either the comma or the point can
be used as the decimal separator symbol.

Next, the results of the different assessed markers from the
Calculation Profile should be entered, in
MoMs (Multiples of the Median as per the
printed report from the laboratory or the sonographer, which
allow the values of these markers to be separated from the
gestation length from which they were determined and from other
variables like the mother's weight, race, etc.).

TRC can only manage 4 calculations or screening profiles,
those outlined at the bottom of the screen (1 for first
trimester and 3 for second trimester). Each calculation can be
carried out if all the required markers have been selected,
such that you will only be able to carry out risk calculations
if the markers for a given profile have been chosen correctly.
The profile type is automatically selected based on the markers
entered before the checkbox is verified.

The checkboxes located directly above the "Compute" button,
labeled "NT Value" and "CRL", unlike the other markers that
require values to be typed in MoMs, allow NT MoMs to be
calculated directly from the NT and the corresponding fetus
length, all in millimeters. The last checkbox should be
selected and the penultimate one unselected (the NT MoMs
checkbox, which, once calculated, will appear to the right of
the ultrasound icon indicating the NT MoMs measurement).

Once all the markers and the maternal age at the EDD have
been entered for a given profile, you can click the "Calculate"
button to send the data to the SBP Soft 2007 server. The server
will carry out the calculations, return the results and present
them at the bottom of the screen, in graphic and numeric
format. 3 parallel bars will appear: the top bar presents the a
priori trisomy 21 risk for maternal age at EDD (the bar will be
in yellow, its length proportional to the risk); the middle bar
presents the trisomy 21 risk calculated from the combination of
the maternal age at EDD and the markers from the given profile
(this bar will be in green when the risk is below the cut-off
level of 1:250, and in red when it exceeds this level, and its
length will be proportional to the risk); and finally the
bottom bar presents the trisomy 18-13 risk, calculated from the
combination of the maternal age at EDD and the markers from the
given profile (variations in color and length are the same as
for the middle bar). It is important to highlight that all the
risks are expressed at term (delivery date), not at screening
date as in some computer programs. In the latter case, the
trisomy 21 risk estimates are between 29 and 50% higher for the
second and first trimester, and the trisomy 18-13 risk
estimates are between 75 and 85% higher in the same
trimesters.

Negative Risk Example:

Positive Risk Example:

Clicking the "Reset" button clears all values entered by the
user and prepares TRC for a new risk calculation.

Scientific basis of
TRC

These days, prenatal screening to evaluate a pregnant
woman’s risk of carrying a trisomy-affected fetus is a very
important aspect of both the prenatal diagnosis of congenital
anomalies and of pregnancy monitoring.

The risk evaluation procedure, or simply risk estimation in
a given pregnancy, consists of a sequence of
mathematical-statistical methods that are successively applied
to obtain a risk index or probability.

TRC calculates the risk using the "likelihood method"
published by Palomaki GE and Haddow JE in ‘Maternal serum
alpha-fetoprotein, age, and Down syndrome risk’ (Am J Obstet
Gynecol 1987;156:460-3). This combines the a priori maternal
age risk, obtained from the meta-analysis by Cuckle HS, Wald NJ
and Thompson SG published in ‘Estimating a woman's risk of
having a pregnancy associated with Down's syndrome using her
age and serum alpha-fetoprotein level’ (Br J Obstet Gynaecol
1987;94:387-2), with the likelihood ratio obtained from the
combined MoMs from the various markers used in each profile,
calculated using the multivariate normal distribution published
by Reynolds TM and Penney MD in ‘The mathematical basis of
multivariate risk screening: with special reference to
screening for Down’s syndrome associated pregnancy’ (Ann Clin
Biochem 1990; 27:452-8).

To calculate multivariate normal distribution we use
"population parameters", which describe the shape of the
Gaussian curve for fetuses affected and not affected by trisomy
21 or 18-13 (mean log 10 and standard deviation), and the
correlation coefficient between each pair of markers included
in the combination or profile. More specifically, for all
second trimester profiles (double, triple and quadruple tests)
that calculate trisomy 21 risk, TRC uses the population
parameters published in the SURUSS trial (Wald NJ, Rodeck C,
Hackshaw AK, Walters J, Chitty L, Mackinson AM in ‘First and
second trimester antenatal screening for Down’s syndrome: the
results of the Serum, Urine and Ultrasound Screening Study
(SURUSS)’, in Health Technol Assess 2003;7(II)); and for the
first trimester, the profile population parameters outlined in
DSQA Tools software (Decision Support Tools for screening QA
Version 2.0 from Media Innovations Ltd, a University of Leeds
and UK National Screening Committee partnership), belonging to
Ellipse 2002 (derived from meta-analyses published by Cuckle
1995, Wald et al 1995, Barkai et al 1993, Nicolaides et al 1998
and Cuckle 2001). For all profiles, in the trisomy 18-13 risk
calculations, we have also taken population parameters from
Ellipse 2002 for consistency with the trisomy 21 calculations.
These population parameters have been chosen as DSQA Tools is a
reputable software validation program for trisomy 21 screening
in the United Kingdom, and therefore all of the risks
calculated by TRC and DSQA Tools coincide exactly.

Intellectual
property

All the intellectual property rights for TRC are reserved to
SBP Soft 2007 S.L. and to the authors of the software. It is
completely prohibited to decompile copies of TRC software or
its documentation for any system that has not been authorized
by the proprietors of the program or their legally authorized
representatives.

TRC VS SsdwLab
5

TRC (Trisomy Risk Calculator) uses the same calculation
engine as SsdwLab 5, which has thoroughly demonstrated
reliability and robustness in over 3 years of clinical use in
many centers across all five continents.

TRC also incorporates an access interface, which is web
compatible with any navigator or current operating system with
Adobe Flash installed. Calculations are carried out on an
online server when the customer’s navigator requests a
calculation and sends the necessary data. Once the calculations
have been carried out, the server sends the customer the
results if it has been possible to calculate them or, if not,
it sends an information message.

This is the modern technology used in the new version,
SsdwLab5 Net, which is in the advanced development stages and
will operate on the Internet and on local networks. An almost
unlimited number of users and centers will be able to work
concurrently on a single installation, and tasks from other
corporate computer systems will be automated, with total
connectivity to external devices like laboratory
auto-analyzers, ultrasound machines, etc.

TRC can be considered a reduced demonstration version of the
wide range possibilities of SsdwLab5 Net. The vast
configuration potential has been limited, as have the new
Gaussian and dichotomic markers, the personalization of
medians, statistical and quality monitoring, the storing of
screening data and perinatal results, and the generation and
personalization of printed reports. Most of these features are
already available in previous versions of our authorized
software for prenatal detection of trisomies and neural tube
defects.

The products SsdwLab 5 and SsdwLab 6
from SBP Soft 2007 S.L. company have been
certified with the EC Full Quality Aassurance
System by the NB 0318.
The SBP Soft 2007 S.L. company has established
and applies a quality management system
according to the standard UNE-EN ISO
13485.

Website of the new version of SsdwLab
prenatal screening software. New user interface
redesigned for web-browser access, multicentre
and multi-user environments and incorporating
many improvements and new features.